Synthesis and biodistribution of two novel99mTc “3+1'mixed ligand complexes as potential brain perfusion agents

Abstract

The research in the last decade has been mainly aimed at the development of technetium-99m radiopharmaceuticals, among which are the "3+1"mixed ligand complexes. Two novel [ 9 9 m Tc]"3+1"mixed ligand complexes each carrying the tridentate ligand, the N-(o-Methylthiophenyl)ethylenediamine or the N-(o-Methylthiophenyl)-β-mercaptoacetamide in combination with monothiolate coligand were produced using stannous chloride as reductant and glucoheptonate as transfer ligand. The identification of [ 9 9 m Tc]-6 and [ 9 9 m Tc]-7 was established by thin layer chromatography. The radiochemical purity of two complexes was over 90%. Biodistribution data in mice showed that both [ 9 9 m Tc]-6 and [ 9 9 m Tc]-7 can penetrate the intact blood-brain barrier and exhibited retention in mice brain. The brain uptakes (%ID/g) were 1.76, 1.17, 0.90 and 0.68, 0.38,0.37 at 2, 30, and 60 minutes i.v. postinjection for [ 9 9 m Tc]-6 and [ 9 9 m Tc]-7, respectively. Examples in this report comfirm us that it is promising to develop 9 9 m Tc complexes as potential brain perfusion agents based on modifying either the tridentate or the monodentate ligands.